crossing96/oncoscreening huggingface dataset:
RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors.	RUNX3 is inactivated at high frequency in many tumors. However, in most cases, inactivation is caused by silencing of the gene due to promoter hypermethylation. Because epigenetic silencing is known to affect many major tumor suppressor genes in cancer cells, it is not clear whether RUNX3 is primarily responsible for the induction of carcinogenesis in these cases, except for the gastric cancer cases that we reported previously. We investigated genetic and epigenetic alterations of RUNX3 in 124 bladder tumor cases and seven bladder tumor-derived cell lines. Here we show that RUNX3 is inactivated by aberrant DNA methylation in 73% (90 of 124) of primary bladder tumor specimens and 86% (six of seven) of bladder tumor cell lines. In contrast, the promoter regions of 20 normal bladder mucosae were unmethylated. Importantly, one patient bore missense mutations, each of which resulted in amino acid substitutions in the highly conserved Runt domain. The mutations abolished the DNA-binding ability of RUNX3. A second patient had a single nucleotide deletion within the Runt domain coding region that resulted in truncation of the protein. RUNX3 methylation was a significant risk factor for bladder tumor development, superficial bladder tumor recurrence, and subsequent tumor progression. These results strongly suggest that inactivation of RUNX3 may contribute to bladder tumor development and that promoter methylation and silencing of RUNX3 could be useful prognostic markers for both bladder tumor recurrence and progression.	bladder
Efficacy of BTA stat, cytology, and survivin in bladder cancer surveillance over 5 years in patients with spinal cord injury.	OBJECTIVES: To evaluate three urine markers, BTA stat, cytology, and urinary survivin levels, in the spinal cord injury (SCI) population. The incidence of bladder cancer in patients with SCI is up to 20 times greater than in the general population. However, bladder cancer biomarkers have not been assessed in this population. METHODS: Between April 1999 and April 2004, 457 patients with SCI enrolled at the HealthSouth Harmarville Rehabilitation Spinal Cord Clinic donated their urine to our SCI urine repository. BTA stat tests and the survivin assay were performed according to published standards. Cytology specimens were sent to our cytopathology laboratory for analysis. RESULTS: A total of 1075 urine specimens from 457 patients were analyzed. Of the 1073 BTA stat tests, 119 showed positive reactions and 954 were negative. In the survivin assays, 47 samples had a score of 1, 38 a score of 2, and 9 a score of 3. No cytology specimens were noted to have malignant cells. During the past 5 years, 3 patients were diagnosed with bladder cancer by cystoscopy and treated for superficial disease. For these patients, none of these three tests (BTA stat, survivin assay, and cytology) was positive before the diagnosis of bladder cancer. CONCLUSIONS: The BTA stat, survivin assay, and urine cytology were unable to predict bladder cancer cases in our cohort of patients with SCI. Cystoscopy, therefore, remains the gold standard for bladder cancer surveillance in patients with SCI.	bladder
Glutathione peroxidase 1 gene polymorphism and risk of recurrence in patients with superficial bladder cancer.	OBJECTIVES: To investigate the potential of genetic polymorphism (Pro198Leu) in the human glutathione peroxidase 1 (hGPX1) gene as a biologic marker predictive of bladder cancer recurrence. Given the high propensity for superficial bladder cancer recurrence, biologic markers that are predictive of recurrence may provide additional helpful information in bladder cancer treatment. To date, few valuable molecular markers have been closely associated with bladder cancer recurrence. METHODS: In this ongoing prospective study, we investigated the potential of genetic polymorphism (Pro198Leu) in the hGPX1 gene, whose protein product is an important metabolic enzyme, as a recurrence predictor. RESULTS: This study included 224 patients with superficial bladder cancer. During a median follow-up of 25.2 months, 138 (61.6%) of the 224 patients experienced disease recurrence. Patients with the hGPX1 wild type had marginally shorter recurrence-free survival compared with those with the hGPX1 variant genotype (log-rank test, P = 0.066). The difference was even greater in whites (log-rank test, P = 0.036). When we performed multivariate analysis using Cox proportional hazards model, we detected a borderline protective role for the hGPX1 variant genotype in recurrence, with a hazard ratio of 0.71 (95% confidence interval 0.48 to 1.05). The protective association was even stronger in whites (hazard ratio 0.63, 95% confidence interval 0.42 to 0.96). CONCLUSIONS: Our findings suggest that a genetic polymorphism in the hGPX1 gene may serve as a molecular marker for monitoring bladder cancer recurrence.	bladder
Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology.	OBJECTIVE: To evaluate patients with a history of transitional cell carcinoma (TCC) of the upper urinary tract (UUT) to determine the incidence, pathological distribution, and risk factors for developing subsequent bladder tumours. PATIENTS AND METHODS: Between 1993 and 2003, 103 patients were treated at our institution for UUT-TCC. We reviewed demographic, clinical, surgical, and pathological data from these patients at a median follow-up of 38.7 months, and used univariate and multivariate analyses with logistic regression modelling to determine prognostic variables for bladder recurrences. RESULTS: In all, 51 (49.5%) patients developed bladder tumours after treatment for UUT-TCC, at a mean interval of 13.2 months. Patient age (P = 0.01), UUT tumour size (P = 0.03), UUT tumour multifocality (P = 0.05), a history of bladder tumours (P = 0.03), and the number of previous bladder tumours (P = 0.05) predicted the development of bladder recurrences on univariate analysis. On multivariate analysis, only a previous history of bladder tumours (odds ratio 2.6, P = 0.05) remained significant. Over 90% of the recurrent bladder tumours were superficial, with two-thirds of these being low to moderate grade. Six patients had muscle-invasive disease, and five had a cystectomy. CONCLUSION: Bladder tumours occurred in half the patients after treatment for UUT-TCC; > 60% of these subsequent bladder tumours were superficial, low- to moderate-grade lesions. Neither the pathology of the UUT tumours nor the method of treatment for the UUT disease was associated with recurrent bladder tumours. Only a history of bladder cancer predicted the development of subsequent bladder tumours.	bladder
[Metastatic brain tumor originating from urachal carcinoma: case report].	The authors presented a patient with metastatic brain tumor originating from urachal carcinoma. A 64-year-old female was admitted to our hospital with complaints of memory disturbance, indifference and apathy of 3 months duration. Head CT and MRI on admission showed a round mass with perifocal edema in the right frontal lobe. After administration of Gd-DTPA, the mass lesion showed ringed enhancement effect. Pelvic MRI scan revealed a bladder tumor, which was diagnosed as urachal carcinoma. The brain lesion was suspected to have metasta sized metastatic from urachal carcinoma, and was excised by craniotomy. Histology of the brain tumor was identical to that of urachal carcinoma. Postoperatively the patient received local radiation therapy, but died of multiple metastasis to lung and local recurrence, 18 months later. Urachal carcinoma is an extremely rare tumor, comprising 0.17-0.34% of all bladder tumors. Though this rare tumor carries a poor prognosis, it may be effective for longer survival of a patient to treat the metastatic brain lesion with surgery and radiation.	bladder
Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model.	PURPOSE: PAD-S31 (13,17-bis (1-carboxypropion) carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl-porphyrin sodium) (Photochemical Co., Ltd., Okayama, Japan), 1 of the latest second-generation photosensitizers, has hydrophilic characteristics and excitation wavelengths of around 670 nm. Using an orthotopic rat bladder tumor model we investigated the biodistribution of PAD-S31 and assessed the antitumor effects of photodynamic therapy (PDT) with PAD-S31. MATERIALS AND METHODS: An orthotopic rat bladder tumor was established by implanting AY-27 cells in the bladder wall. After intravenous PAD-S31 administration the accumulation of PAD-S31 in the tumor and normal bladder wall was investigated by a fluorometric technique. One or 3 hours after intravenous administration of PAD-S31 (5 mg/kg) bladder tumors in rats were transurethrally irradiated at 100 mW/cm with a light dose of 50 to 200 J/cm. The efficacy of PDT was evaluated 7 days later by observation with an ultrathin cystoscope and histopathological examination. RESULTS: The ratio of PAD-S31 concentration in tumor tissue to that in normal bladder wall was more than 1 at all time points and it achieved a maximum (more than 10) 150 to 240 minutes after PAD-S31 administration. All rats that were irradiated at 100 J/cm 3 hours after PAD-S31 administration showed more than 50% tumor destruction. When the light dose was more than 150 J/cm, more than half of the rats showed complete tumor eradication, of which the average size was 6 mm. CONCLUSIONS: We report that PDT using PAD-S31 is effective for destroying bladder tumors in an orthotopic rat model. These experimental results suggest that this therapy could be a clinically promising method for the treatment of patients with bladder cancer.	bladder
Quality of life after cystectomy and urinary diversion: an evidence based analysis.	PURPOSE: We critically examined the evidence supporting the widely accepted notion that patients undergoing continent urinary tract reconstruction after cystectomy experience superior quality of life outcomes than patients receiving a conduit. MATERIALS AND METHODS: Based on a comprehensive MEDLINE literature search we retrieved and evaluated all full-length articles published in the English, French, German, Italian and Spanish languages comparing conduit diversion with continent cutaneous diversion and/or orthotopic bladder substitution with respect to quality of life or similar concepts. All studies were rated according to the International Consultation on Urological Diseases modification of Oxford Center for Evidence-Based Medicine levels of evidence. RESULTS: The literature on quality of life after radical cystectomy for bladder cancer was rather extensive but generally of questionable quality. The main problems were flaws in the patient materials and methodologies used. To our knowledge not a single randomized, controlled study exists in the field. Because only few articles achieved a level of evidence better than III, the International Consultation on Urological Diseases rating system does not allow further differentiation among studies. Most studies showed that overall quality of life after cystectomy remained good in most patients irrespective of urinary diversion type. CONCLUSIONS: Existing studies are unable to prove that continent reconstruction after radical cystectomy is superior to conduit diversion. This review emphasizes the importance of performing well designed studies in the future.	bladder
Unusual CT findings in urachus carcinoma with an extensive and atypical pattern of metastasis. A case report.	Carcinoma of the urachus is very rare. Usually it has a typical appearance on computed tomography, with calcifications in a midline supravesical mass, but advanced stages of this neoplasm require malignancy evaluation that is not easy to establish. We report a case of a urachal tumor where CT scan did not properly assess the response to chemotherapy, while it did show an uncommon metastatic localization in the laterocervical soft tissues.	bladder
EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival.	We sought to evaluate the biological function of the receptor tyrosine kinase EphB4 in bladder cancer. All of the nine bladder cancer cell lines examined express EphB4 and the receptor could be phosphorylated following stimulation with its cognate ligand, EphrinB2. Out of the 15 fresh bladder cancer specimens examined, 14 expressed EphB4 with a mean sevenfold higher level of expression compared to adjacent normal urothelium. EphB4 expression was regulated by several mechanisms: EPHB4 gene locus was amplified in 27% tumor specimens and 33% cell lines studied; inhibition of EGFR signaling downregulated EphB4 levels; and forced expression of wild-type p53 reduced EphB4 expression. EphB4 knockdown using specific siRNA and antisense oligodeoxynucleotides molecules led to a profound inhibition in cell viability associated with apoptosis via activation of caspase-8 pathway and downregulation of antiapoptotic factor, bcl-xl. Furthermore, EphB4 knockdown significantly inhibited tumor cell migration and invasion. EphB4 knockdown in an in vivo murine tumor xenograft model led to a nearly 80% reduction in tumor volume associated with reduced tumor proliferation, increased apoptosis and reduced tumor microvasculature. EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy.	bladder
Clinical relevance of serum angiogenic activity in patients with transitional cell carcinoma of the bladder.	Angiogenesis is essential for tumor growth and progression and is mediated by positive and negative regulators of vessel growth. Since angiogenic mediators found in patient serum have been postulated to reflect the angiogenic potential of a malignant tumor, we investigated the angiogenic activity in the serum of patients with transitional cell carcinoma (TCC). The data were correlated to tumor characteristics and the clinical course of the patients. Eighty-one patients with transitional cell carcinoma and 53 control persons were included in the study. Preoperative serum samples were collected and both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified by ELISA. Additionally, the serum evoked proliferative activity on human umbilical vein endothelial cells (HUVEC) was evaluated. Data were compared to the clinical course of the patients. Serum of tumor patients significantly enhanced the proliferative capacity of HUVEC, compared to cells grown in standard culture medium (p = 0.0032), but not when compared to serum from control persons. Serum from patients with superficial TCC and well differentiated tumors induced a significantly higher angiogenic response (ANG(hi)) than serum from patients with poorly differentiated and invasive carcinomas (ANG(lo); p = 0.037). VEGF level of ANG(hi) serum was 384.22 +/- 247.76 pg/ml (n = 37) which significantly differed from mean VEGF level detected in ANG(lo) serum (247.72 +/- 211.93 pg/ml, n = 42; p = 0.019). Similarly, mean bFGF levels were 9.58 +/- 5.91 pg/ml in ANG(hi) serum versus 5.74 +/- 3.52 pg/ml) in ANG(lo) serum (p = 0.0043). A negative correlation was established between VEGF/bFGF serum concentration and patient prognosis. The experiments demonstrate a positive correlation between VEGF and bFGF serum level and endothelial proliferation in vitro. The inverse relationship between angiogenic activity and tumor stage might disclose information about angiogenesis and tumor progression in TCC.	bladder
[Construction and expression of single chain Fv antibody against human bladder carcinoma].	OBJECTIVE: To construct and express single chain Fv antibody against human bladder carcinoma, which was expected to have advantages in targeted diagnosis and therapy with the characteristics of lower immunogenicity. METHODS: Hybridoma BDI-1 cell, which secreted a monoclonal antibody against human bladder carcinoma, was used to isolate total RNA. By reverse transcription, the cDNA was synthesized and used as templates for amplifying the immunoglobulin heavy-and light-chain variable region genes by polymerase chain reaction (PCR). The amplified DNA was ligated into a sequencing vector pUC19 and sequenced with Sanger's method. The VH and VL genes were inserted into expression vector pFUW80. By inducing, the ScFv antibodies were expressed and secreted from Escherichia coli. Binding activities against the bladder carcinoma cells were detected by ELISA. The 5 x his-tagged ScFv antibodies were purified on IDA-Ni2+ resin by immobilized metal chelate affinity chromatography (IMAC). The purified ScFv antibodies were analyzed by SDS-PAGE. RESULTS: A full-length of VH and VL genes was 366 and 324 base pairs respectively. Comparing with other published sequences, the VH gene was a member of mouse heavy-chain VH subgroup II and originated from re-arrangement of VH, Dsp2.2 and JH4; the VL gene was VK subgroup IV and from Vk and Jk4. The ScFv antibodies could inhibit 84% of the antigen binding activity of original McAb BDI-1. The purified ScFv antibodies gave a single major band (Mr-29 000) on SDS-PAGE. CONCLUSION: The single chain Fv antibody against human bladder carcinoma was successfully constructed and expressed.	bladder
Detection of malignancy in cytology specimens using spectral-spatial analysis.	Despite low sensitivity (around 60%), cytomorphologic examination of urine specimens represents the standard procedure in the diagnosis and follow-up of bladder cancer. Although color is information-rich, morphologic diagnoses are rendered almost exclusively on the basis of spatial information. We hypothesized that quantitative assessment of color (more precisely, of spectral properties) using liquid crystal-based spectral fractionation, combined with genetic algorithm-based spatial analysis, can improve the accuracy of traditional cytologic examination. Images of various cytological specimens were collected every 10 nm from 400 to 700 nm to create an image stack. The resulting data sets were analyzed using the Los Alamos-developed GENetic Imagery Exploitation (GENIE) package, a hybrid genetic algorithm that segments (classifies) images using automatically 'learned' spatio-spectral features. In an evolutionary fashion, GENIE generates a series of algorithms or 'chromosomes', keeping the one with best fitness with respect to a user-defined training set. First, we tested the system to determine if it could recognize malignant cells using artificial cytology specimens constructed to completely avoid the requirement for human interpretation. GENIE was able to differentiate malignant from benign cells and to estimate their relative proportions in controlled mixtures. We then tested the system on routine cytology specimens. When targeted to detect malignant urothelial cells in cytology specimens, GENIE showed a combined sensitivity and specificity of 85 and 95%, in samples drawn from two separate institutions over a span of 4 years. When trained on cases initially diagnosed as 'atypical' but with unequivocal follow-up by biopsy, surgical specimen or cytology, GENIE showed efficiency superior to the cytopathologist with respect to predicting the follow-up result in a cohort of 85 cases. We believe that, in future, this type of methodology could be used as an ancillary test in cytopathology, in a manner analogous to immunostaining, in those situations when a definitive diagnosis cannot be rendered based solely on the morphology.	bladder
Optimization of the MB49 mouse bladder cancer model for adenoviral gene therapy.	Bladder cancer is regarded as a promising candidate for innovative therapies in the field of immune and gene therapy. In this paper, we present the subcutaneous, metastatic and a novel orthotopic model of murine MB49 bladder cancer in C57BL/6 mice. We further show the potential of using adenoviral vectors together with different transduction enhancers to augment in vivo gene delivery. Finally, we present candidate genes for tumour detection, therapy or targeting. The MB49 tumour grew rapidly in mice. The subcutaneous model allowed for tumour detection within a week and the possibility to monitor growth rate on a day-by-day basis. Injection of MB49 cells intravenously into the tail vein gave rise to lung metastases within 16 days, while instillation of tumour cells into pretreated bladders led to a survival time of 20-40 days. Adenoviral vectors can be used as a vehicle for gene transfer to the bladder. By far, the most potent transduction enhancer was Clorpactin, also known as oxychlorosene. Last, we show that MB49 cells express tumour-associated antigens like bladder cancer-4, prostate stem cell antigen and six-transmembrane epithelial antigen of the prostate. Given the possibility for efficient genetic modification of the bladder and the presence of known tumour antigens, the MB49 models can be used in innovative ways to explore immunogene therapy.	bladder
CD10 immunohistochemical staining in urothelial neoplasms.	CD10, or common acute lymphoblastic leukemia antigen, is a cell surface neutral endopeptidase that inactivates various bioactive peptides. It is expressed by hematopoietic cells and their neoplasms and in a variety of nonhematopoietic tissues and neoplasms. CD10 has been suggested as a useful marker for urothelial carcinoma, but the few studies of CD10 in urothelial tissues have shown varying results; a comparative study of the CD10 immunoprofile in a range of urothelial tumors has not been performed. We report the CD10 immunoprofile of 70 cases representing urothelial lesions as defined by the World Health Organization Classification (2004) of urothelial neoplasia. We demonstrated moderate to strong CD10 immunohistochemical staining in 67% (40/60) of urothelial neoplasms, with a predominantly cytoplasmic staining pattern. We found a statistically significant difference in staining intensity (scale, 0-3) between high-grade neoplasms (mean, 2.5), dysplasia (mean, 1.7), and low-grade lesions (mean, 1.3), with the high-grade group showing a propensity for a more diffuse staining distribution than the low-grade group. Larger studies incorporating molecular genetic techniques should help better define the role of CD10 in urothelial tumorigenesis.	bladder
[Urological cancer].	We reported laparoscopic adrenalectomy for adrenal cancer, our experience of laparoscopic partial nephrectomy, radical prostatectomy, retroperitoneal lymph node dissection for testicular cancer. Minimally invasive therapy is the direction of progress in current clinical medicine, so laparoscopic procedures have developed and their application has expanded in the urological field.	bladder
Do patients with frank haematuria referred under the two-week rule have a higher incidence of bladder cancer?	INTRODUCTION: The new NHS guaranteed that everyone with suspected cancer would be able to see a specialist within 2 weeks of their GP deciding that they need to be seen urgently. We investigated whether referrals under the two-week rule for frank haematuria results in a clinically significant advantage over normal referral pathways in patients with suspected bladder cancer. PATIENTS AND METHODS: Patients referred for frank haematuria specifically under the two-week cancer rule were prospectively recorded over a 2-year period. Results of haematuria investigations were compared to a control group of routine frank haematuria referrals. RESULTS: Of the 32 patients in each group, four bladder cancers were found in the 2-week rule group and five bladder cancers were found in the control group (P > 0.05). The number of other demonstrable urological causes of frank haematuria was also the same in the two groups. CONCLUSIONS: The incidence of bladder cancer and other urological pathologies is the same irrespective of referral pattern. It is not clear whether seeing such patients within 2 weeks confers any clinically significant advantage over conventional referral pathways. Not all patients with macroscopic haematuria are referred or seen under the two-week rule, this has considerable clinical governance implications for all departments of urology.	bladder